The complement system is part of the innate immune system that enhances the ability of antibodies and phagocytic cells to clear microbes and damaged cells. It consists of over 30 proteins and fragments produced by the liver and found in blood serum. There are three pathways of complement activation: the classical pathway triggered by antibody-antigen interaction, the lectin pathway triggered by mannose-binding lectin, and the alternative pathway triggered by spontaneous activation of complement proteins. All three pathways result in the formation of the membrane attack complex that causes cell lysis. Complement deficiencies are associated with increased susceptibility to certain bacterial infections.

1. THE COMPLEMENT
SYSTEM
GROUP 11

2. GROUP MEMBERS
• Vanessa Ohui Dadeboe UE20015417
• Priscilla Bandah UE20014517
Koomson Abigail UE20016917

3. OBJECTIVES
• History
• Overview of the complement system.
• Functions
• Three main pathways
• Regulation
• Role in disease
• References

4. HISTORY
• Discovered in the 1890’s by Jules Bordet, a young
Belgian scientist in Paris.
• She said the serum has two components. The heat
stable component responsible for specific immunity
and the heat sensitive component responsible for non-
specific immunity.
• Paul Ehrlich named the heat-sensitive component
complement.

5. OVERVIEW
• The complement system is a part of the innate immune system
that enhances the ability of antibodies and phagocytic cells to
clear microbes and damaged cells from an organism.
• It can be activated by antibodies generated by the adaptive
immune system
• It is a defensive system consisting of over 30 proteins and protein
fragments produced by the liver and found in circulating blood
serum.
• It functions in a cascade system.
• Complement proteins are often designated by “C”. From C1 –
C9.

6. OVERVIEW CONTINUED
• Proteolysis results in large fragments “b” and smaller
fragments “a”. Eg. C3a and C5b
• The only exception is C2, where C2a is the large fragment
and C2b is the smaller fragment.

7. FUNCTIONS

8. PATHWAYS
1. CLASSICAL PATHWAY
• Triggered by Ag – Ab interaction. Ab used are
IgM and IgG.
• C1 complex is activated when it binds to the ends
of antibodies.
• Once C1 is activated, it activates C2 and C4 by
cutting them in halves giving C2a and C2b, C4a
and C4b.
• C2b and C4b bind to form a C3 activation
complex on the surface of the bacteria while the
C2a and C4a diffuse away.

9. PATHWAYS CONTINUED
• The C3 activation complex activates C3
proteins by cutting them into C3a and C3b.
• C3b is an opsonin that binds to and coat the
surface of the bacteria.
• Opsonization increases phagocytosis by
1000 fold.
• C3a increases inflammatory response.
• Eventually enough C3b is cleaved or halved
that the surface of the bacteria begins to
become saturated with it.

10. PATHWAYS CONTINUED
• C2b and C4b which make up the C3
activation complex has a slight affinity
for C3b and hence C3b binds to them.
• When C3b binds to C2b and C4b it
forms a new complex referred to as the
C5 activation complex.
• The C5 activation complex activates C5
proteins by cutting them into C5a and
C5b
• C5b begins to coat the surface of the
bacteria because many are produced.
• C5a disperses away from the bacteria.

11. PATHWAYS CONTINUED
• C5b on the surface of bacteria binds to C6
• The binding of C6 to C5b activates C6 so that it can
bind to C7
• C7 binds to C8 which in turn binds to many C9’s
• Together these proteins form a circular complex called
the Membrane attack complex (MAC).
• The MAC causes Cytolysis.
• The circular membrane attack complex acts as a channel in
which cytoplasm can rush out of and water rushes in.
• The cells inner integrity is compromised and it dies

12. PATHWAYS CONTINUED
2. ALTERNATIVE PATHWAY
• It is slower than the classical pathway.
• Activated by C3b binding to microbial cell surfaces.
• C3 contains an unstable thioester bond which slows spontaneous
hydrolysis to C3b and C3a.
• C3b is able to bind to foreign surface antigens.
• The C3b on the surface of a foreign cell binds to another plasma
protein called Factor B.

13. PATHWAYS CONTINUED
• The binding of C3b to factor B allows a protein
enzyme called Factor D to cleave Factor B to
Ba and Bb.
• Factor Bb remains bound to C3b while Ba and
Factor D disperse away.
• Properdin, also called factor P, binds to the
C3bBb complex to stabilize it.
• C3bBbP make up the C3 activation complex for
the alternative pathway

14. PATHWAYS CONTINUED
• The C3 activation complex causes the
production of more C3b.
• This allows the initial steps of this pathway to
be repeated and amplified.
• When an additional C3b binds to the C3
activation complex it converts it into a C5
activation complex.
• The C5 activation complex cleaves C5 into C5a
and C5b.
• C5b begins the production of the MAC.

15. PATHWAYS CONTINUED
3. LECTIN PATHWAY
• Lectins are carbohydrate binding proteins.
• It is similar to the classical pathway but with the opsonin, mannose-
binding lectin (MBL) and ficolins instead of C1q.
• Activated by the binding of MBL to mannose residues which activates
the MBL associated serine proteases, MASP-1 and MASP-2 which is
similar to C1r and C1s respectively.
• This complex activates C2 and C4 by cutting them into C2a and C2b,
C4a and C4b.
• C4b binds to C2b to form the C3-convertase as in the classical
pathway.

16. REGULATION

17. ROLE IN DISEASES
COMPLEMENT DEFICIENCY
• Example, deficiency in the MAC components of complements is
associated with Neisseria meningitidis and N. gonorrhoeae which are
bacterial infections.
COMPLEMENT REGULATORS DEFICIENCY
• Example, mutations in the complement regulators like factor H and
membrane cofactor protein have been associated with atypical
hemolytic uremic syndrome.
Other examples are Paroxysmal nocturnal hemoglobinuria, asthma,
Alzheimer’s disease, multiple sclerosis and rejection of transplanted
organs.

18. REFERENCES
• Roitt I, Brostoff J, Male D (2001). Immunology (6th ed), 480p. St. Louis:
Mosby, ISBN 0-7234-3189-2
• Parham P (2005). The immune system. New York: Garland, ISBN 0-
8153-4093-1
• DeFranco AL, Locksley RM, Robertson M (2007). Immunity: The
immune response in infectious and inflammatory disease. London;
Sunderland, MA: New Science Press; Sinauer Associates, ISBN 987-0-
9539181-0-2.
• Stoemer, Kristina A, Morrison, Thomas E. (15 March 2011).
Complement and Viral pathogenesis, Virology. 411 (2): 362-373
Central.